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Coronavirus disease 2019 (COVID-19) is characterized by an acute respiratory infection with multisystem involvement and the association of its severity to liver function abnormalities is not well characterized. The aim of this study was to assess the association between the severity of COVID-19 patients and liver function abnormalities. This retrospective study included adult patients with confirmed COVID-19, which were classified as non-severe or severe according to World Health Organization guidelines. Liver function test results were compared between the severity groups. A total of 339 patients were included of which 150 (44.25%) were severe cases. The male-to-female ratio was 0.9:1 and 3:2 in the non-severe and severe groups, respectively (p=0.031). Aspartate aminotransferase (AST), alanine transaminase (ALT), and total bilirubin levels and acute liver injury (ALI) incidence were significantly higher in the severe group compared to non-severe group (p<0.001, p<0.001, p=0.025, p=0.014, respectively). In contrast, albumin levels were significantly lower (p=0.001). Multivariate analysis showed that ALI was significantly associated with human immunodeficiency virus (HIV) infection (odds ratio (OR): 5.275; 95% confidence interval (CI): 1.165-23.890, p=0.031), hemoglobin level (OR: 1.214; 95%CI: 1.083-1.361, p=0.001), and hypoalbuminemia (OR: 2.627; 95%CI: 1.283-5.379, p=0.008). Pre-existing liver diseases were present in 6.5% of patients. No significant differences were observed between the groups based on COVID-19 severity and ALI presence. Liver function test abnormalities, including ALI, are more prevalent in patients with severe COVID-19 infection. HIV infection, high hemoglobin levels, and hypoalbuminemia may be potential risk factors for ALI.

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INTRODUCTION: We assessed chronic liver disease (CLD)-related mortality in the U.S. using death data (2011-2021) obtained from National Vital Statistics System (NVSS). The average annual percentage change (AAPC) from the models selected by Joinpoint regression analysis over the pre-pandemic (2011-2019) and the 2019-2021 were reported because non-linear trend in death rates were observed over the 2011-2021. Liver-specific death was defined as an underlying cause of death and Chronic liver disease (CLD)-related death was defined as any cause of death. During the pre-pandemic, age-standardized HCC- and cirrhosis-specific death rates were annually increased by AAPC = +1.18% (95% confidence interval, 0.34% to 2.03%) and AAPC = +1.95% (1.56% to 2.35%). In contrast, during the 2019-2021, the AAPC in age-standardized cirrhosis-specific death rate (per 100,000) accelerated by up to AAPC +11.25% (15.23 in 2019 to 18.86 in 2021) whereas that in age-standardized HCC-specific death rate slowed to -0.39 (-1.32% to 0.54%) (3.86 in 2019 to 3.84 in 2021). Compared to HCC-specific deaths, cirrhosis-specific deaths were more likely to be non-Hispanic white (72.4% vs. 62.0%) and non-Hispanic American Indian and Alaska native (AIAN) (2.2% vs. 1.1%) and have NAFLD (45.3% vs. 12.5%) and ALD (27.6% vs. 22.0%). During the 2019-2021, the age-standardized HCV- and HBV-related death rate stabilized, whereas the age-standardized NAFLD- and ALD-related deaths rate increased to 20.16 in 2021 (AAPC = +12.13% [7.76% to 16.68%]) and to 14.95 in 2021 (AAPC = +18.30% [13.76% to 23.03%]), which were in contrast to much smaller incremental increases during the pre-pandemic (AAPC = +1.82% [1.29% to 2.35%] and AAPC = +4.54% [3.97% to 5.11%]), respectively). The most pronounced rise in the age-standardized NAFLD-related death rates during the pandemic was observed among AIAN (AAPC = +25.38%), followed by non-Hispanic White female (AAPC = +14.28%), whereas the age-standardized ALD-related death rates during the pandemic were highest among AIAN (AAPC = +40.65%), followed by non-Hispanic Black female (AAPC = +26.79%). CONCLUSIONS: COVID-19 pandemic had a major negative impact on cirrhosis-specific and CLD-related mortality in the U.S. with significant racial and gender disparities.

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OBJECTIVE: Liver function test (LFT) abnormalities are higher in patients with severe COVID-19. Most of the studies on this theme were conducted in foreign nations, and the association with LFT abnormalities was not sufficiently addressed in the study areas. Therefore, the current study aimed to investigate the effects of COVID-19 infection on liver function of patients. SETTING: A facility-based comparative cross-sectional study was carried out from 10 April to 15 June 2022, among COVID-19 infected individuals admitted in Eka Kotebe General Hospital and Saint Petrous Specialized Hospitals, Addis Ababa, 2022. PARTICIPANTS: A total of 284 confirmed COVID-19-positive and COVID-19-negative controls matched by gender and age were included in the present study. RESULTS: Among SARS-COV-2 positive groups, 63 (44.4%) had one or more LFT abnormalities. The most common elevated level of the LFTs among patients with COVID-19 were gamma-glutamyl transferase (GGT) 50 (35.2%), while the most common lowered level was albumin 58 (40.8%). The mean values of aspartate aminotransferase (AST) (35.4±26.9 vs 22.9±12.6, p<0.001) were significantly different between patients with COVID-19 and the COVID-19-free groups. Being COVID-19-positive was significantly associated with an elevated level of AST (AOR=3.0, 95% CI 1.2 to 7.4) and GGT (AOR=4.55, 95% CI 2.02 to 10.3). Being male was significantly associated with an elevated level of total bilirubin (BILT, AOR=2.41, 95% CI 1.2 to 4.9) and direct bilirubin (BILD, AOR=3.7, 95% CI 1.72 to 8.2), and also severe stage of COVID-19 was associated with hypoalbuminaemia (AOR=3.3, 95% CI 1.4 to 7.9). SARS-COV-2 infection was independently associated with LFT abnormality. CONCLUSION: Patients with COVID-19 had decreased albumin levels, and elevated AST, GGT, BILT and BILD levels.

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BACKGROUND: Conflicting evidence exists regarding the effects of ursodeoxycholic acid (UDCA) on coronavirus disease 2019 (COVID-19). This study investigates the association between UDCA administration and COVID-19 infection and its related outcomes in individuals with chronic liver disease (CLD). METHODS: A customized COVID-19 research database (n = 3,485,376) was created by integrating data from the National Health Insurance Service (NHIS) and the Korea Disease Control and Prevention Agency's COVID-19 databases. The study focused on patients diagnosed with COVID-19 in 2021, using the NHIS data from 365 days before diagnosis. To create comparable groups with and without UDCA administration before COVID-19, we used propensity score matching. The primary endpoint was the first confirmed positive result for severe acute respiratory syndrome coronavirus-2. In addition, we identified severe COVID-19-related outcomes. Subgroup analysis were conducted based on the dose of UDCA exposure. RESULTS: Data from 74,074 individuals with CLD was analyzed. The participants' average age was 57.5 years, and 52.1% (19,277) of those in each group were male. Those with prior UDCA exposure had a significantly lower risk of COVID-19 infection (adjusted OR: 0.80, 95% CI [0.76-0.85]) compared to the non-UDCA group. Additionally, the UDCA group had a lower risk of severe COVID-19 outcomes (adjusted OR: 0.67, 95% CI [0.46-0.98]). Subgroup analyses indicated that there was a decrease in COVID-19 infection and its related outcomes with increasing UDCA exposure dose. CONCLUSIONS: Our large observational study highlights the potential use of readily available UDCA as an adjunctive therapy for COVID-19 in individuals with CLD.

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Advanced chronic liver disease (ACLD) is associated with a wide spectrum of immune dysfunction. The clinical impact of SARS-CoV-2 on the development of decompensation and immune response in unvaccinated outpatients has not as yet been clearly defined. This study aimed to evaluate the clinical and immunological impact of SARS-CoV-2 on outpatients with ACLD. This is an observational case-control study, in which ACLD outpatients were included prospectively and consecutively and classified into two groups: SARS-CoV-2 infected and non-infected. Patients' baseline characteristics and infection data were collected and analyzed. Immunoglobulin G (IgG) levels against Spike 1 were evaluated. The primary endpoint was risk of liver decompensation during follow-up, assessed after propensity score matching and adjusted by Cox regression. Between October 2020 and July 2021, ACLD outpatients (n = 580) were identified, and 174 patients with clinical follow-up were included. SARS-CoV-2 infection incidence was 7.6% (n = 44). Risk of liver decompensation was significantly higher after infection (HR = 2.43 [1.01-5.86], p = 0.048) vs. non-infection. The time of IgG evaluation was similar in all patients (n = 74); IgG concentrations were significantly higher in compensated vs. decompensated patients (1.02 ± 0.35 pg/mL vs. 0.34 ± 0.16 pg/mL, p < 0.0001) and correlated with hemoglobin levels. The dysregulation of the innate immune response in patients with decompensated liver disease increased the risk of further decompensation following SARS-CoV-2, mainly due to a worsening of ascites.

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OBJECTIVE: To explore the incidence of liver function test derangement, the precise patterns of derangement, and their relationship with coronavirus disease-2019 pneumonia severity. METHODS: The retrospective study was conducted at the Dow University Hospital and the Ojha Institute of Chest Diseases, Karachi, and comprised consecutive data from December 16, 2020, to March 16, 2021, of adults of either gender who had nasal swabs positive for coronavirus disease-2019 on real-time reverse transcriptase-polymerase chain reaction. Data regarding patients' demographics, co-morbidities, addictions, laboratory results, and standard information was retrieved from electronic and manual records. The severity of the disease was determined based on World Health Organisation protocols. Data was analysed using SPSS 23. RESULTS: Of the 344 patients, 235(68.3%) were males and 109(31.7%) were females. The overall mean age was 54.58±14.75 years, 187(54.4%) had severe coronavirus disease-2019 pneumonia and 157(45.6%) had non-severe disease at the time of admission. There was a significant prevalence of both mixed and cholestatic patterns of liver function test abnormality among the cases (p=0.046). The presence of a mixed pattern was linked to the disease severity (p<0.05). Advanced age and hypertension were significant risk factors for the development of severe coronavirus disease-2019 pneumonia (p<0.001 and p=0.002). CONCLUSIONS: Liver function test abnormality and coronavirus disease-2019 pneumonia severity were fund to have a significant relationship.

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Trastuzumab emtansine (T-DM1) is widely utilized as a second-line and subsequent treatment for metastatic HER2+ breast cancer and has shown promise in early breast cancer treatment, particularly in adjuvant settings for residual disease after neoadjuvant chemotherapy. However, concerns have arisen regarding long-term hepatic adverse drug reactions (ADRs) not identified in clinical trials. We investigated potential safety signals of T-DM1 in hepatobiliary disorders and the time-to-onset of ADRs using the FDA Adverse Event Reporting System (FAERS) database. Suspected ADRs were extracted and divided into two groups: T-DM1 (N = 3387) and other drugs (N = 11,833,701). Potential signal for T-DM1 in hepatobiliary disorder were identified (reporting odds ratio [ROR] = 5.66, 95% confidence interval [CI] = 5.11-6.27; information component [IC] = 2.35, 95% Credibility Interval [Crl] = 2.18-2.51). A breast cancer indicated subgroup analysis (2519 T-DM1; 172,329 other drugs) also identified a potential safety signal (ROR = 3.28, 95% CI = 2.92-3.68; IC = 1.53, 95%CrI = 1.35-1.71). The median time-to-onset for T-DM1-associated hepatobiliary disorders was 41 days. For prolonged and chronic hepatobiliary disorders, median times were 322.5 and 301.5 days, respectively. These findings highlight the need for further research to inform clinical decisions on optimal T-DM1 treatment duration, balancing benefits with potential adverse reactions.

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The association between air pollutants and hepatobiliary pancreatic diseases remains inconclusive. This study analyzed up to 247,091 participants of White European ancestry (aged 37 to 73 years at recruitment) from the UK Biobank, a large-scale prospective cohort with open access. An air pollution score was utilized to assess the combined effect of PM2.5, PM2.5-10, PM10, NO2, and NOX on total hepatobiliary pancreatic diseases, liver diseases, cholecyst diseases, and pancreatic diseases. Cox proportional hazard models were employed to evaluate the relationships between air pollutants and the incidence of these diseases. Restricted cubic spline regressions were used to examine the dose-response association between air pollutants and the risk of hepatobiliary pancreatic diseases. We identified 4865 cases of total hepatobiliary pancreatic diseases, over a median follow-up of 10.86 years. The air pollution scores were moderately associated with increased liver disease risk (HR = 1.009, 95 % CI: 1.004, 1.014), but not with cholecyst and pancreatic diseases. Among the individual air pollutants, PM2.5 (HR = 1.069, 95 % CI: 1.025, 1.115) and PM10 (HR = 1.036, 95 % CI: 1.011, 1.061) significantly increased liver disease risk. Males showed a higher risk of liver diseases with PM2.5 (HR = 1.075, 95 % CI: 1.015, 1.139). Additionally, individuals with overweight (HR = 1.125, 95 % CI: 1.052, 1.203), age ≥ 60 and ≤73 (HR = 1.098, 95 % CI: 1.028, 1.172), and alcohol intake ≥ 14 unit/week (HR = 1.078, 95 % CI: 1.006, 1.155) had a higher risk of developing liver diseases at high expose to PM2.5. This study suggests that prolonged exposure to ambient air pollutants may elevate the risk of liver diseases.

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'Westernization', which incorporates industrial, cultural and dietary trends, has paralleled the rise of noncommunicable diseases across the globe. Today, the Western-style diet emerges as a key stimulus for gut microbial vulnerability, chronic inflammation and chronic diseases, affecting mainly the cardiovascular system, systemic metabolism and the gut. Here we review the diet of modern times and evaluate the threat it poses for human health by summarizing recent epidemiological, translational and clinical studies. We discuss the links between diet and disease in the context of obesity and type 2 diabetes, cardiovascular diseases, gut and liver diseases and solid malignancies. We collectively interpret the evidence and its limitations and discuss future challenges and strategies to overcome these. We argue that healthcare professionals and societies must react today to the detrimental effects of the Western diet to bring about sustainable change and improved outcomes in the future.

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BACKGROUND AND AIMS: Alcohol use disorder has been reported in patients undergoing bariatric procedures, but the pattern of alcohol consumption has not been evaluated. We investigated the prevalence, risk factors, and impact of binge drinking (BD) at the time of surgery and during follow-up. METHODS: A prospective, longitudinal study of subjects undergoing bariatric surgery was included in the LABS-2 registry between 2006 and 2009. Participants with AUDIT questionnaire at the time of surgery and a minimum of 12 months follow-up were included. BD was defined as consuming ≥5 drinks on at least 1 occasion in the previous month. Liver biopsies were obtained during bariatric procedures in not all cases. Survival analysis was performed with the adjusted Cox regression model and competing risk. RESULTS: A total of 2257 subjects were included, with a median follow-up of 79 months. The prevalence of BD at time of surgery was 12%, and it raised up to 23% during follow-up. Patients with BD predominantly had a binge eating disorder (OR=1.35 [95% CI: 1.04-1.76]), regularly consumed fast food [OR=1.4 (95% CI: 1.07-1.85)] and used other drugs (OR=2.65 [95% CI: 1.74-4.04]). Within liver biopsies evaluation, BD showed higher hepatic iron deposits (OR=3.00 [95% CI: 1.25-7.21]). BD at the time of surgery was associated with a higher risk of BD during follow-up (OR=10.49 [95% CI: 7.86-14.00]) and long-term mortality (HR: 3.21 [95% CI: 1.67-6.18]). Specific causes of death in these patients with BD were liver disease (p=0.020), suicide (p=0.015), neoplasms (p=0.034), and respiratory (p=0.025). CONCLUSIONS: The prevalence of BD in patients undergoing bariatric surgery is high and increases the risk of postoperative liver disease, suicides, and long-term mortality.

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BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a significant health problem. Dietary intervention plays an important role in patients with MAFLD. OBJECTIVES: We aimed to provide a reference for dietary patterns in patients with MAFLD. METHODS: The presence of MAFLD was determined in the United Kingdom Biobank cohort. Nine dietary pattern scores were derived from the dietary records. Multivariable Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). The contrast test was employed to calculate the heterogeneity across MAFLD statuses. RESULTS: We identified 175,300 patients with MAFLD at baseline. Compared with non-MAFLD, MAFLD was significantly associated with chronic liver disease (CLD) (HR: 3.48; 95% CI: 3.15, 3.84), severe liver disease (SLD) (HR: 2.87; 95% CI: 2.63, 3.14), liver cancer (HR: 1.93; 95% CI: 1.67, 2.23), and liver-related death (LRD) (HR: 1.93; 95% CI: 1.67, 2.23). In the overall cohort, the alternate Mediterranean diet (aMED) (HRCLD: 0.53; 95% CI: 0.37, 0.76; HRSLD: 0.52; 95% CI: 0.37, 0.72), planetary health diet (PHD) (HRCLD: 0.62; 95% CI: 0.47, 0.81; HRSLD: 0.65; 95% CI: 0.51, 0.83), plant-based low-carbohydrate diet (pLCD) (HRCLD: 0.65; 95% CI: 0.49, 0.86; HRSLD: 0.66; 95% CI: 0.51, 0.85), and healthful plant-based diet index (hPDI) (HRCLD: 0.63; 95% CI: 0.47, 0.84; HRSLD: 0.61; 95% CI: 0.47, 0.78) were associated with a lower risk of CLD and SLD. Additionally, unhealthful plant-based diet index (uPDI) was associated with increased risk of CLD (HR: 1.42; 95% CI: 1.09,1.85), SLD (HR: 1.50; 95% CI: 1.19, 1.90), and LRD (HR: 1.88; 95% CI: 1.28-2.78). The aforementioned associations remained consistently strong within the MAFLD subgroup while exhibiting less pronounced in the non-MAFLD group. However, no significant heterogeneity was observed across different MAFLD statuses. CONCLUSIONS: These findings highlight the detrimental effects of MAFLD on the development of subsequent liver diseases and the importance of dietary patterns in managing MAFLD.

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BACKGROUND: Disability and chronic diseases are prevalent conditions associated with mortality, but little information is available on their potential synergistic effects. OBJECTIVE: This study aimed to describe additive interactions between disability and chronic diseases on mortality risk in middle-aged and older adults. METHODS: A representative cohort of 22,800 community-dwelling Spanish people aged 50 years or older were interviewed for disability with the Global Activity Limitation Indicator and specific chronic diseases in the 2011-12 and 2014 National Health Surveys and subsequently followed up for mortality. Five-year all-cause mortality risks were standardized in each disability-by-comorbidity category through inverse probability weighting. We computed interaction contrasts as the departure of the standardized risk difference for people with both conditions from the sum of the standardized risk differences for those with any single condition. RESULTS: The baseline prevalence of disability was 35.1 % (95 % confidence interval [CI] 34.4 %, 35.9 %). There was compelling evidence of synergistic effects of disability with chronic liver disease, heart diseases other than myocardial infarction, cancer, and cerebrovascular disease, with large positive interaction contrasts (95 % CIs) of 106.7 (-16.4, 229.9), 45.7 (6.9, 84.5), 45.1 (-15.0, 105.2), and 42.9 (-41.0, 126.9) excess deaths per 1000 persons. Less clear synergistic responses were observed for other comorbidities. We found some evidence of antagonism for osteoporosis, with a negative interaction contrast of -18.0 (95 % CI -82.2, 46.2) deaths per 1000 persons. CONCLUSION: Given the high mortality risk in people with disability, the study of its synergistic effects with target comorbidities can provide relevant information regarding preventive measures.

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Liver diseases have a global prevalence of 25%, accounting for 4% of all deaths worldwide, and are associated with a 36% increased risk of fatal and nonfatal cardiovascular events. Metabolic dysfunction-associated steatotic liver disease constitutes the liver expression of metabolic syndrome and represents the primary type of liver disease. Microscopical analysis of biopsies, which allows the evaluation of a small portion of tissue with inferences made to the entire organ, is considered the gold standard for determining the presence of liver diseases. However, potential sampling errors in liver biopsies are conceivable because the obtained tissue represents only a tiny fraction of the entire liver mass and may not accurately reflect the true pathological state. Studies have demonstrated the existence of sampling errors in liver biopsies, particularly concerning the severity of inflammation, degree of fibrosis, and the presence of cirrhosis. Also, clinical studies have shown that histopathological abnormalities are better detected in humans when liver samples are collected from both the right and the left lobes. However, a gap exists in clinical investigation to clarify the role of differences between these lobes in improving the diagnostic and prognostic for liver diseases. Building upon the heterogeneous nature of pathological alterations observed in liver lobes, this perspective review provided recommendations to enhance the precision of diagnosis and prognostic accuracy of liver diseases.

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The aim of this research was to define the prevalence of antibodies against hepatitis D virus (anti-HDV Ab) in a group of 26 outpatients with liver dysfunction in northeastern Bulgaria. Serum samples were obtained from April 2022 to December 2023 in the "Status" Medical Diagnostic Laboratory, Varna, Bulgaria. We found seroprevalence of anti-HDV Ab in 15.4% (CI: 4.3-34.8%) of the target population. Age and gender had no significant role in HDV seropositivity.

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INTRODUCTION: A novel indicator of inflammation is the systemic immune-inflammation index (SII), and liver dysfunction is linked to the advancement of inflammation. In light of this, this study aims to look into any potential connections between SII and markers of liver injury. METHODS: A cross-sectional study was conducted using the National Health and Nutrition Examination (NHANES) dataset for 2017-2020. The linear relationship between SII and markers of liver injury was examined using multiple linear regression models. Examining threshold effects and fitted smoothed curves were utilized to describe nonlinear connections. RESULTS: A total of 8213 adults aged 18-80 years participated in this population-based study. In the fully adjusted model, SII maintained a negative association with ALT(ß = -0.003, 95%CI:-0.005, -0.002, P<0.00001), AST(ß = -0.004, 95% CI:-0.005, -0.002, P<0.00001), and GGT(ß = -0.004, 95% CI:-0.007, -0.000, P = 0.03791) and a positive association with ALP (ß = 0.005, 95% CI:0.003, 0.007, P<0.00001). In subgroup analyses, it was found that SII remained negatively correlated with ALT, AST and GGT in gender, age and body mass index. SII was positively correlated with ALP at BMI≥25(kg/m2)(ß = 0.005, 95% CI:0.003, 0.008, P = 0.00001), and was negatively correlated with ALT(ß = -0.004, 95% CI:-0.005, -0.002, P<0.00001), AST(ß = -0.004, 95% CI:-0.005, -0.003, P<0.00001) and GGT(ß = -0.004, 95% CI:-0.008, -0.000, P = 0.02703) at BMI≥25, whereas no significant correlation was observed at BMI<25 (all P-values>0.05). Furthermore, the association between SII and markers of liver injury was nonlinear. By using a two-stage linear regression model for analysis, a U-shaped relationship was found to exist between SII and ALT with a turning point of 818.40(1,000 cells/µl). The inflection points of SII with AST and GGT were 451.20 (1,000 cells/µl) and 443.33 (1,000 cells/µl), respectively, and no significant inflection point with ALP was observed. Interaction tests demonstrated that SII correlation with ALT, AST, ALP, and GGT was not significantly different between strata (all p for interaction>0.05). CONCLUSIONS: The research findings suggested that there was a negative correlation between SII and ALT, AST and GGT, and a positive correlation with ALP. However, larger prospective investigations are still greatly needed to confirm the findings.

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Liver diseases, including non-alcoholic fatty liver disease (NAFLD), are a growing global health issue. Environmental exposure to toxic metals can harm the liver, increasing the risk of NAFLD. Essential elements are vital for liver health, but imbalances or deficiencies can contribute to the development of NAFLD. Therefore, understanding the interplay between toxic metals and essential elements in liver disease is important. This study aims to assess the individual and combined effects of toxic metals (lead(Pb), cadmium (Cd), mercury (Hg)), and essential elements (manganese and selenium) on the risk of liver disease. Methods: We assessed the individual and combined effects of Pb, Cd, Hg, manganese (Mn), and selenium (Se) on liver disease risk using data from the National Health and Nutrition Examination Survey between 2017 and 2018. We performed descriptive statistics and linear regression analysis and then utilized Bayesian Kernel Machine Regression (BKMR) techniques such as univariate, bivariate, and overall effect analysis. BKMR enabled the assessment of non-linear exposure-response functions and interactions between metals and essential elements. Posterior Inclusion Probabilities (PIPs) were calculated to determine the importance of each metal and essential element in contributing to liver disease. Regarding our study results, the regression analysis of liver injury biomarkers ALT, AST, ALP, GGT, total bilirubin, and the FLI-an indicator of NAFLD-with toxic metals and essential elements, adjusting for covariates such as age, sex, BMI, alcohol consumption, ethnicity, income, and smoking status, demonstrated the differential effects of these contaminants on the markers of interest. Our BKMR analysis provided further insights. For instance, the PIP results underscored Pb's consistent importance in contributing to liver disease (PIP = 1.000), followed by Hg (PIP = 0.9512), Cd (PIP = 0.5796), Se (PIP = 0.5572), and Mn (PIP = 0.4248). Our univariate analysis showed a positive trend with Pb, while other exposures were relatively flat. Our analysis of the single-variable effects of toxic metals and essential elements on NAFLD also revealed that Pb significantly affected the risk of NAFLD. Our bivariate analysis found a positive (toxic) trend when Pb was combined with other metals and essential elements. For the overall exposure effect of exposure to all the contaminants together, the estimated risk of NAFLD showed a steady increase from the 60th to the 75th percentile. In conclusion, our study indicates that Pb exposure, when combined with other toxic metals and essential elements, plays a significant role in bringing about adverse liver disease outcomes.

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PURPOSE: To determine the incidence of newly diagnosed liver disorders (LD) up to 3.5-year post-acute COVID-19, and risk factors associated with new LD. METHODS: We analyzed 54,699 COVID-19 patients and 1,409,547 non-COVID-19 controls from March-11-2020 to Jan-03-2023. New liver disorders included abnormal liver function tests, advanced liver failure, alcohol and non-alcohol related liver disorders, and cirrhosis. Comparisons were made with ambulatory non-COVID-19 patients and patients hospitalized for other lower respiratory tract infections (LRTI). Demographics, comorbidities, laboratory data, incomes, insurance status, and unmet social needs were tabulated. The primary outcome was new LD at least two weeks following COVID-19 positive test. RESULTS: Incidence of new LD was not significantly different between COVID-19 and non-COVID-19 cohorts (incidence:1.99% vs 1.90% p>0.05, OR = 1.04[95%CI: 0.92,1.17], p = 0.53). COVID-19 patients with new LD were older, more likely to be Hispanic and had higher prevalence of diabetes, hypertension, chronic kidney disease, and obesity compared to patients without new LD. Hospitalized COVID-19 patients had no elevated risk of LD compared to hospitalized LRTI patients (2.90% vs 2.07%, p>0.05, OR = 1.29[0.98,1.69], p = 0.06). Among COVID-19 patients, those who developed LD had fewer patients with higher incomes (14.18% vs 18.35%, p<0.05) and more with lower incomes (21.72% vs 17.23%, p<0.01), more Medicare and less Medicaid insurance, and more patients with >3 unmet social needs (6.49% vs 2.98%, p<0.001) and fewer with no unmet social needs (76.19% vs 80.42%, p<0.001). CONCLUSIONS: Older age, Hispanic ethnicity, and obesity, but not COVID-19 status, posed increased risk for developing new LD. Lower socioeconomic status was associated with higher incidence of new LD.

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BACKGROUND AND AIMS: Chronic liver diseases belong to the most common diseases worldwide and are associated with increased morbidity and mortality. Although more than one in three adults are estimated to have metabolic dysfunction-associated steatotic liver disease (MASLD), awareness of this condition is low amongst the general public, health care professionals and policy makers. However, meaningful knowledge transfer is essential for raising awareness and improving prevention and treatment. This study set out to investigate the use of the major internet search engine to understand how knowledge transfer has evolved by analyzing liver-related searches trends. METHODS: We investigated Google search trends by measuring the number of hits relating to liver diseases between 2004 and 2021 in seven languages and European countries but also worldwide. All analyses were performed in R using the R Google trends package gtrendsR. RESULTS: We found that interest in MASLD [formerly non-alcoholic fatty liver disease (NAFLD)] has generally increased over time, but that interest in metabolic associated steatohepatitis (MASH) - the most severe form of MASLD - has decreased. Interest in viral hepatitis C has decreased, whereas the number of queries regarding viral hepatitis B have been stable but dominated by interest in vaccination for it. Recent medical developments (in viral hepatitis) did not lead to a noticeable change in overall search behavior. Users preferred searching using their native language and less complex medical terms and acronyms (e.g., fatty liver instead of NAFLD). CONCLUSIONS: In the last two decades, Google search trends have followed the general development in the field of hepatology. Searches were dominated by non-experts and are not being rapidly influenced by novel scientific developments. Also, users preferred search terms in their native languages rather than English and tended to avoid complex medical search terms. Awareness and communication strategies around MASLD should consider these preferences when addressing the general public.

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BACKGROUND: The burden of chronic liver disease (CLD) deaths attributable to the hepatitis B virus (HBV) and hepatitis C virus (HCV) remains unknown. Further research is required to elucidate the extent of this burden in the eventual elimination of these diseases. METHODS: Data on liver cancer, cirrhosis, and other CLD among 204 countries and territories between 1990 and 2019 was extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) published in 2019. The Bayesian age-period-cohort model was used to analyze the temporal trend and predict the disease burden by 2030. RESULTS: The number of HCV-related CLD deaths surpassed that of CLD deaths caused by HBV in 2019 (536833 deaths versus 523003 deaths) and is expected to be maintained until 2030 (689124 deaths versus 628824 deaths). East Asia had the highest burden of chronic HBV and HCV infections during the study period. In 2019, the largest age-standardized death rates (ASDR) of CLD deaths caused by HBV and HCV were mainly observed in Western Sub-Saharan Africa (18.75%) and Eastern Sub-Saharan Africa (16.42%), respectively. South Asia and East Asia are predicted to have the highest number of CLD deaths related to HCV and HBV by 2030. Eastern Europe and South Asia show the largest expected increase in disease burden caused by HCV or HBV between 2019 and 2030. No GBD region is projected to achieve the WHO target of a 65% reduction in mortality from chronic HBV and HCV infections by 2030. CONCLUSIONS: Although the mortality of CLD caused by HBV and HCV decreased in the last three decades (from 1990 to 2019), the number of deaths will continue to increase until 2030. Therefore, governments and international organizations need to strengthen the effectiveness of vaccines, screening, and treatment, especially in potential emerging hotspot regions.

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